Long-term prognosis of patients with an SCN5A loss-of-function variant and progressive cardiac conduction disorder or Brugada syndrome.

Background: The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown.

Objective: This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events.

Methods: Probands and family members with (likely) pathogenic SCN5A loss-of-function variants were retrospectively included.

Diagnosis of Brugada Syndrome With a Sodium-Channel-Blocker Test: Who Should Be Tested? Who Should Not?

Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not.

Catheter Ablation for Ventricular Tachycardia in Patients With Desmoplakin Cardiomyopathy.

Background: Desmoplakin (DSP) pathogenic/likely pathogenic (P/LP) variants are associated with malignant phenotypes of arrhythmogenic cardiomyopathy (DSP-ACM). Reports of outcomes after ventricular tachycardia (VT) ablation in DSP-ACM are scarce.

Objectives: In this study, the authors sought to report on long-term outcomes of VT ablation in DSP-ACM.

Are disease-specific patient-reported outcomes measures (PROMs) used in cardiogenetics? A systematic review.

Patient-reported outcome measures (PROMs) are used to facilitate patient-centered care (PCC). While studies in patients with cardiac conditions have revealed poorer health-related quality of life (HRQoL) and elevated emotional stress, studies in inherited cardiac conditions (ICC) seem rare. A systematic review evaluated which (specific domains of) PROMs are used in patients with ICC.

Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.

Background: MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives: This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Novelties in Brugada Syndrome: Complex Genetics, Risk Stratification, and Catheter Ablation.

Brugada syndrome (BrS) is an inherited arrhythmia syndrome with distinctive electrocardiographic abnormalities in the right precordial leads and predisposes to ventricular arrhythmias and sudden cardiac death in otherwise healthy patients. Its complex genetic architecture and pathophysiological mechanism are not yet completely understood, and risk stratification remains challenging, particularly in patients at intermediate risk of arrhythmic events. Further understanding of its complex genetic architecture may help improving future risk stratification, and advances in management may contribute to alternatives to implantable cardioverter-defibrillators.

Importance of exercise stress testing in evaluation of unexplained cardiac arrest survivor.

Background: In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required.

Methods: We describe 3 survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission.

Results: All 3 patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest-related heart rate-corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up.

Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome.

The diagnosis of Brugada syndrome (BrS) requires the presence of a coved (Type 1) ST segment elevation in the right precordial leads of the electrocardiogram (ECG). The dynamic nature of the ECG is well known, and in patients with suspected BrS but non-diagnostic ECG at baseline, a sodium channel blocker test (SCBT) is routinely used to unmask BrS. There is little doubt, however, that in asymptomatic patients, a drug-induced Brugada pattern is associated with a much better prognosis compared to a spontaneous Type 1 ECG.

Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) associated with relevant left ventricular (LV) structural or functional traits.

Cardiac Repolarization in Health and Disease.

Abnormal cardiac repolarization is at the basis of life-threatening arrhythmias in various congenital and acquired cardiac diseases. Dysfunction of ion channels involved in repolarization at the cellular level are often the underlying cause of the repolarization abnormality. The expression pattern of the gene encoding the affected ion channel dictates its impact on the shape of the T-wave and duration of the QT interval, thereby setting the stage for both the occurrence of the trigger and the substrate for maintenance of the arrhythmia.

Multimodality Screening For (Peri)Myocarditis In Newly Diagnosed Idiopathic Inflammatory Myopathies: A Cross-Sectional Study.

Background: Cardiac involvement in idiopathic inflammatory myopathy (IIM or "myositis") is associated with an approximate 4% mortality, but standardised screening strategies are lacking.

Objective: We explored a multimodality screening on potentially reversible cardiac involvement -i.e.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin () Truncating Variant.

Background: Truncating variants in desmoplakin (tv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of tv cardiomyopathy.

Methods: Individuals with tv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers.

Deep phenotyping of two preclinical mouse models and a cohort of RBM20 mutation carriers reveals no sex-dependent disease severity in cardiomyopathy.

cardiomyopathy is an arrhythmogenic form of dilated cardiomyopathy caused by mutations in the splicing factor RBM20. A recent study found a more severe phenotype in male patients with cardiomyopathy patients than in female patients. Here, we aim to determine sex differences in an animal model of cardiomyopathy and investigate potential underlying mechanisms.

KBTBD13 is a novel cardiomyopathy gene.

KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.

Clinical applicability of artificial intelligence for patients with an inherited heart disease: A scoping review.

The number of inherited heart disease (IHD) studies using artificial intelligence (AI) has increased rapidly over the last years. In this scoping review, we aimed to present an overview of the current literature available on the applicability of AI within the field of IHD. The literature search resulted in eighteen articles in which an AI model was trained and tested, mostly for diagnostic and predictive purposes.

Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to cause these conditions, but evidence supporting these gene-disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT and SQTS patients, we applied an evidence-based reappraisal of previously reported genes.

The β-angle can help guide clinical decisions in the diagnostic work-up of patients suspected of Brugada syndrome: a validation study of the β-angle in determining the outcome of a sodium channel provocation test.

Aims: In patients with Brugada syndrome (BrS) but without spontaneous Type-1 electrocardiogram, several electrocardiographic characteristics have been studied, including the β-angle. Previous studies suggested that the β-angle might be useful in distinguishing BrS-patients from patients with only suggestive repolarization patterns without performing sodium channel blocker provocation testing. In this study, we aimed to determine the diagnostic value of the β-angle in patients suspected of BrS.